Magnetic resonance imaging (MRI) contrast agents that contain gadolinium chelates continue to play a critical role in the evaluation of diseases of the central nervous system including primary and secondary neoplasia, infection (HIV), vascular disorders (aneurysms), cerebral infarction and white matter disease (multiple sclerosis). Gadolinium-enhanced MR has also shown some promise in characterizing hepatic and extrahepatic abdominal lesions, and possibly also for discriminating benign from malignant lesions in the breast. Qualitative assessments of MRI enhancement patterns have, however, provided only limited pathophysiological insights. Recently, considerable research efforts have been directed at the use of MRI for the quantitative assessment of physiologic parameters such as the blood-brain barrier permeability and the relative volume of the extracellular space (ECS). Kinetic models of tissue and plasma Gd concentration allow these physiologic parameters to be extracted from dynamic MR signal data. One common assumption used in such models is that the in vivo relaxivity of Gd-chelates is similar to that measured in vitro (in saline). The first aim of this proposal is to test this assumption using MR measurements of spin-lattice and spin-spin relaxation rates before and after administration of Gd-chelate in a freezing rat brain lesion, in conjunction with ICP-atomic emission spectroscopic measurements of tissue Gd levels. Preliminary work indicates that the in vivo Gd relaxivity in damaged tissue is several times higher than the Gd relaxivity measured in saline. Derivation of clinical MR-based quantitative measures of blood-brain barrier permeability will therefore require an in vivo determination of in vivo relaxivity. The second aim of this proposal is to show that estimates of relaxivity may be based on an independent measure of ECS (provided by an in vivo measurement of the apparent diffusion coefficient in the brain lesion). Preliminary results suggest that ADC is highly correlated with the ECS volume. An important consequence of this work will be the ability to differentiate between lesions that appear similar in the MR image, but differ significantly in their permeability and relaxivity. Another significant outcome will be that MRI measurements of in vivo relaxivity in the damaged tissues will permit determination of the optimum Gd dose and MRI parameters.